Shark cartilage has traditionally been credited with a number of medical benefits but it is primarily marketed for its anticancer effects [1-5]. The potential value of shark cartilage in cancer treatment as an angiogenesis inhibitor [6-8] has been investigated and several clinical trials have been done or are underway. However, its efficacy has been controversial thus far [9-14].
In addition, there have been a number of other bioactivities attributed to shark cartilage, including beneficial effects on osteoarthritis, rheumatoid arthritis, progressive systemic sclerosis and neurovascular glaucoma, just to name a few [15-17]. There are suggestions that shark cartilage also contains anti-inflammatory agents and wound healing substances [15, 18, 19]. There has been speculation, rather than scientific evidence, that shark cartilage may stimulate the cellular and humoral components of the immune system, presumably making it effective against tumor growth and bacterial, viral and fungal infections. Several shark cartilage preparations claiming immune-boosting effects are on the market (Cartilade™ from Cartilage Technologies Inc.; SC Formula, from Nature's Sunshine, etc). An extract of shark liver has recently been found to stimulate the immune system [20] and Rosen et al [21] reported on immunoregulatory effects of a bovine cartilage preparation (CatrixS™). They disclose that fractions with 0-10 KD and 30-100 KD range enhanced T-dependent and T-independent antibody responses in vivo, possibly related to the chondroitin sulfate component.
A variety of shark cartilage products have been introduced as dietary supplements or even tested in clinical practice, however, many of the claims of purity, bioactivity and clinical efficacy are not backed by rigorous scientific investigation. Although there has been progress in the understanding of the field, the isolation, purification, analysis and standardization of these materials are still extremely challenging.
There has been controversy as to whether shark cartilage could be effective via oral administration. The active principles of shark cartilage described in the literature and believed to be behind various activities are biopolymers, usually proteins. Pettit and Ode isolated two glycoproteins from shark cartilage: sphyrnastatin 1 and 2 [22]. McGuire et al demonstrated antiproliferative activity of a heat stable, <10 KD fraction of shark cartilage extract on endothelial cell population [4]. This is in agreement with Oikawa's work, where a substance with an average molecular mass of 1-10 KD was isolated from shark cartilage. Oikawa's material was heat stable, however no information on the composition of the substance was given and the material was not administered orally [23]. Suzuki et al isolated from shark cartilage a fraction of large molecular mass inhibiting solid tumor growth [24]. Another preparation, a patented anti-inflammatory substance isolated from shark cartilage, was of molecular mass larger than 100 KD [25], however this substance was not intended for oral administration.
Proteins have low oral bioavailability and short in vivo half-lives, which to date have necessitated their delivery by infusion or frequent injections [26]. In the case of antigen delivery, biodegradable and biocompatible microspheres have been used for antigen delivery into the GI tract [27]. Conventional wisdom says that biopolymers would be either disintegrated into monomers, or smaller or larger oligomers, and thus lose biological activity, (a classical problem with protein or peptide based pharmaceuticals), or if they remained unchanged or were cleaved into large non-absorbable fragments, they would be incapable of exerting their biological effect due to physical barrier.
Except for the reports from questionable clinical trials and other anecdotal evidence [28, 29, 30] there are only a limited number of published scientific papers demonstrating biological effects due to oral administration of shark cartilage preparations. As an example, one study demonstrated a positive effect of shark cartilage on the survival time of rats with implanted intracranial tumor [31].
The protein and carbohydrate components of shark cartilage extracts come largely from proteoglycans (PG) and represent up to 50% of its dry weight [32]. Cartilage also contains collagen and glycosaminoglycans (GAGs), including chondroitins A, B, and C. The GAG part of PG is known to inhibit proliferation of fibroblasts. A number of GAGs, such as heparin and heparan sulfate, have been shown to interact with a wide range of growth factors and cytokines, including α-FGF, β-FGF, GM-GSF, IL-1a, IL1b, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, hIL-10, vIL-10 and INF-γ. This interaction has been shown to be important in modulating the activity of these growth factors. Shark cartilage contains PGs, GAGs (e.g. CHS A, 1 and C) and collagen. PGs stimulate the immune system, which works synergistically with protein to fight disease [33].
Proteoglycans might be involved in the interaction of primitive, hematopoietic progenitor cells and stromal cells. IL-3 and GM-GSF can be bound by heparan sulfate. PGs form bone-marrow stromal cells or their extracellular matrix and can be presented in a biologically active form of hematopoietic cells. Proteoglycans might also be involved in cell adhesion and homing of hematopoietic stem and progenitor cells [34].